Table of Contents
- Network Refinement Process
- Pediatric, Adolescent, Maternal HIV Research
- Interoperable Sites to Address Infectious Disease Outbreaks
- Funding, Partnerships, and Strategy
- Data Sharing and Interoperability
- HIV Vaccine Research
- Co-Infections and Co-Morbidities
Is there a deadline for submitting comments and questions?
NIAID anticipates that the comment period will conclude in December 2017, prior to concept approval by the NIAID AIDS Research Advisory Committee. In the coming months, NIAID will be hosting a series of webinars to discuss, build, and refine the research agenda. In addition, there will be many opportunities for formal and informal discussions, including at the upcoming network meetings.
What advice would you give the current clinical research sites to begin preparing for these anticipated changes?
It is very important for the site and unit investigators and research community to provide input on what scientific questions need to be addressed for 2020 and beyond. Also, we encourage the sites to stay connected to DAIDS and the current networks and to remain active in the process.
Please elaborate on the planned integration of pediatric, adolescent, and maternal research questions within the three high-priority focus areas (non-vaccine prevention, vaccines, and therapeutics).
Many of the research questions for prevention, vaccines, and therapeutics that need to be addressed in 2020 and beyond are relevant to both adolescents and adults. For example, research on HIV cure and TB will be relevant across the age spectrum. It is important to distinguish which questions are unique to distinct age groups. We must also take into account expected research progress and developments between now and the renewal date. By answering those questions, we can begin to determine the size, scope, and direction of the research agenda for each age group. We are seeking input from you to determine the most relevant and impactful questions in these defined areas of research and age groups, which will help focus the future research agenda.
Is the current structure of having a separate network for pediatric, adolescent, and maternal research expected to continue beyond 2020?
We are taking into account the scientific questions that need to be addressed in 2020 and beyond. Currently assessments of those questions indicate that a network dedicated to pediatric, adolescent and maternal research may not be the most strategic method of delivering the innovative, efficient results needed to turn the corner on the HIV/AIDS pandemic. Moving forward, NIH is seeking to create an integrated network model that will cover adults, pediatrics, adolescents, and pregnant women in the areas of vaccines, prevention, and therapeutics.
You mentioned that pediatric vaccines were part of the agenda. Can you elaborate on how you see work on pediatric vaccines intersecting with the Vaccine and Treatment Evaluation Units?
As one example, within NIH and NIAID, there are several groups working to develop and evaluate RSV vaccines. NIAID has used the HIV/AIDS clinical research sites and the Vaccine and Treatment Evaluation Units (VTEUs) to evaluate RSV vaccines through the IMPAACT network. We have worked to pair the best sites—those affiliated with either IMPAACT or VTEUs—with the appropriate research protocols. This will ensure that the sites selected for a particular protocol (e.g., the next generation of RSV vaccines) will be robust, effective enrollers.
Historically, research on adolescents, pregnant women, and HIV-infected children has not been prioritized within the more adult areas of focused treatment or vaccines. How will NIAID ensure that prioritization is given to the meaningful inclusion of these populations in NIAID-supported research?
The high-priority questions that need to be addressed in HIV-infected children, adolescents and pregnant women will ultimately drive the research agenda. For example, the single most important thing we can accomplish for HIV-infected children is to evaluate the best drugs that are currently licensed and used in adults so they can be given safely and easily to infants and children. While some trials are underway now, others still require partnerships with industry to move forward. This needs to be a top priority as we approach 2020. With respect to adolescents and prevention, we need to consider enrolling this population in the clinical trials of injectable cabotegravir where it is legal and ethical to do so. Some networks, such as the Microbicides Trials Network, have already begun pursuing enrollment of young children in research.
Can you expand on the role of the networks in non-HIV diseases such as Ebola and Zika?
The NIAID HIV/AIDS clinical trials networks have played an important role in addressing non-HIV infectious diseases. For example, during the pandemic flu outbreak, the IMPAACT network ran a series of Phase I clinical trials to evaluate the safety and immunogenicity of the H1N1 vaccine in HIV positive pregnant women and adolescent children. Since there is a significant amount of expertise in non-HIV infectious diseases within NIH and NIAID, the currently funded HIV/AIDS clinical trials networks could play a bigger role in this area in the future. With the understanding that each outbreak will have its own unique challenges, the networks and any sites that are located in areas affected by future outbreaks should be ready and available the need arises. NIAID will continue to use the pay-as-you-go process of renting facilities such as network labs or data management systems.
Is the malaria vaccine in HIV infected/at risk populations a priority?
While malaria has not been a high priority for the HIV/AIDS clinical trials networks, it is something to consider in the future depending on the efficacy results of several Phase III malaria vaccine studies. The networks currently do not have a site footprint in areas endemic with malaria. This would be a good example of where the networks could use a pay-as-you-go model with DMID sites or other sites to perform such trials.
Will non-HIV research be integrated into NIAID clinical sites, such as the antibiotic resistance research group from DMID?
There is great promise in using the HIV/AIDS clinical trial networks to conduct research that addresses infectious disease issues. As the research agenda develops, DMID and DAIDS will discuss site location, capacity, and availability for future non-HIV studies. For example, it may be possible for the VRC to use the network sites on a pay-as-you-go model for studies involving Zika and other infectious diseases.
How do you see funding across the three scientific areas (vaccines, non-vaccine prevention, and therapeutics) evolving compared with current funding levels?
Availability of NIH funding will largely depend on scientific priority and the compelling nature of the research agenda. Funding levels change as new, costly, large Phase IIb and III trials launch. NIAID is working on a dynamic pricing model to assist with allocating funds to high-priority scientific opportunities.
Will NIAID have a full agenda, or will each of the individual research areas—vaccines, non-vaccine prevention, and therapeutics—continue to have their own agendas that are developed independently?
NIAID encourages collaboration and sharing of data and information across the HIV/AIDS research field. There have been many instances of overlap on product development and evaluation. For example, broadly neutralizing antibodies (bNAbs) are being evaluated for prevention, direct intervention, and treatment. If we are using a product in three different spheres of research, we need to find a way to more easily evaluate the aggregate safety data without having to go into three different data streams. For this to occur, we need better collaboration, not forced integration.
You seem to suggest that non-infectious co-morbidities will need partnerships in order to be studied. Does this mean NIAID will need funding from other institutes?
HIV/AIDS research is supported across many NIH institutes. NIAID does not always have the expertise needed to address specific co-morbidities. Other institutes can bring the expertise and funding needed for a particular study, such as in the previously mentioned REPRIEVE trial. In these situations, NIAID can provide the network infrastructure, oversight of clinical trials, monitoring pharmacy, and related functions.
Many of the initiatives described require the development of drugs and vaccines that can only be manufactured and distributed by the pharmaceutical industry. How does DAIDS intend to partner with industry to assure development and approval of the most promising interventions?
Partnerships among NIAID, the clinical trials networks, and industry are incredibly important to ensure that we continue to see progress in developing vaccines and therapeutic and prevention interventions. NIAID relies on the intellectual power, creativity, and problem solving capacities of the network leadership, investigators, and committee members to obtain and evaluate the best products available from industry. One example is injectable cabotegravir, which is now being evaluated in HPTN 083 in collaboration with ViiV Healthcare. Also, a number of HIV vaccines being manufactured by industry partners are being developed and evaluated in HIV Vaccine Trials Network (HVTN) studies. Moving forward, the key is to lay the groundwork needed at the concept level so industry will be more willing to participate.
How will NHLBI, NIDDK, and other NIH Institutes be engaged for collaborations going forward? Will they participate in the RFA, or will this need to be negotiated by the network?
NIAID will be using the model previously employed to involve other institutes: leveraging the NIH Office of AIDS Research (OAR) to identify institutes willing to tackle strategic challenges that overlap with their interests. Since NIAID is not the expert on non-HIV issues such as diabetes or cardiovascular disease, we rely on OAR to help us find partners within NIH. Several sponsored meetings already have led to the formation of some partnerships. As research agendas develop and focus on specific areas, these collaborations will be critical for the next steps.
Do you envision a standard data-management platform for all sites and networks, including non-HIV networks?
NIAID has taken some steps in this direction. We have started to require the Statistical and Data Management Centers to produce Clinical Data Interchange Standards Consortium-compatible datasets, and part of this effort involves the implementation of a platform called Medidata Rave. We will evaluate and consider whether additional standardization will improve overall interoperability.
Would results as expected, or even negative results, from P5 vaccine trials help inform our HIV vaccine research agenda?
All study results will help inform the future research agenda. For example, the results of the ongoing HVTN 702 trial, which is currently evaluating the safety and efficacy of the RV144-modified vaccine regimen, will impact any additional studies planned in 2020 and beyond. Many of the current studies will have results before 2020, and the research agenda, particularly with regard to HIV cure, TB prevention, and HIV vaccines and prevention, must have a degree of flexibility to account for these results.
Can you expand a bit on the role of the existing NIH HIV/AIDS clinical trials networks in research on non-HIV disorders?
The NIH HIV/AIDS clinical trials networks play an important role in addressing non-HIV co-morbidities. A prime example is the NHLBI-NIAID REPRIEVE study, which is a large multicenter international study designed to evaluate whether statins can reduce the risk of major cardiovascular events. This study demonstrates how we utilize our research infrastructure and leadership to effectively address important co-morbidities.
You emphasized TB as an HIV co-infection. Will studies of TB be conducted only in co-infected people, or will studies in TB mono-infected people also be pursued? What about viral hepatitis?
Based on the funding structure at NIAID, DAIDS is responsible for tackling co-infections such as TB. However, DAIDS is aware that data and results from studies involving HIV-TB co-infected people may also be relevant to TB mono-infected people. There are opportunities for collaboration with other parts of NIAID, including the Division of Microbiology and Infectious Diseases (DMID) and Division of Intramural Research, with the goal of having a more integrated approach to tackle diseases such as TB that affect mono-infected and co-infected populations. Viral hepatitis is another important co-infection that needs to be discussed and considered for the agenda. The possible strategy moving forward may be to focus on therapeutics and prevention of hepatitis B. Another area of particular interest is HIV-induced inflammation, and residual disease where inflammation is the underlying cause of the non-infectious co-morbidities.
Do we expect to see a different kind of association between HIV and TB programs, especially as related to forms of TB immunotherapy?
NIAID is moving towards an integrated approach for tackling TB. A process needs to be developed for setting a broader TB agenda that covers improved treatment, vaccine development, and potential immunotherapy.